Diagnostic Yield of Electroencephalography in the Medical and Surgical Intensive Care Unit

Background

To determine the incidence of electrographic seizures during continuous electroencephalography (cEEG) in the medical and surgical ICU.

Methods

We retrospectively reviewed the records of all adults who underwent cEEG in our medical and surgical ICU over a 4.5 year period. Patients with acute brain injury were excluded. Our primary outcome was cEEG documentation of an electrographic seizure, defined as a rhythmic discharge or spike and wave pattern demonstrating definite evolution and lasting at least 10 s. To assess inter-rater variability in cEEG interpretation, two electrophysiologists independently reviewed all available cEEGs of subjects with electrographic seizures documented on their clinical cEEG report and those of an equal number of randomly selected subjects from the remaining cohort.

Results

Kappa analysis showed a value of 0.88, indicating excellent inter-rater agreement. Electrographic seizures were identified in 12 of 105 patients (11 %, 95 % CI 5–18 %). This rate did not change after excluding patients with a history of seizure, remote brain injury, or seizure-like events before cEEG. In an ordinal logistic regression model controlling for age, sex, and SOFA score, electrographic seizures were associated with lower odds of good outcomes on the Glasgow Outcome Scale at discharge (OR 0.3, 95 % CI 0.1–0.8).

Conclusion

In a tertiary care medical and surgical ICU, electrographic seizures were seen on 11 % of cEEGs ordered for the evaluation of encephalopathy, and were associated with worse functional outcomes at discharge. Our findings confirm the results of a prior study suggesting a substantial burden of electrographic seizures in critically ill encephalopathic patients.     

Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation

Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau’s ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation.     

Mitochondrial function in human brains is affected by pre‐ and post mortem factors

G. Harish, C. Venkateshappa, A. Mahadevan, N. Pruthi, M. M. S. Bharath and S. K. Shankar (2013) Neuropathology and Applied Neurobiology 39, 298–315 Mitochondrial function in human brains is affected by pre‐ and post mortem factors Aim: Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre‐ and post mortem factors, we investigated the effect of these variables on mitochondrial function. Methods: We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n = 45) was affected by increased storage time (11.8–104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5–26 h), gender difference and agonal state [based on Glasgow Coma Scale: range = 3–15] in the frontal cortex, as a prototype. Results: We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P = 0.005; succinate dehydrogenase: P = 0.01; mitochondrial reductase: P = 0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r = ?0.40; P = 0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P = 0.003), while the activity of glutathione‐S‐transferase declined with increased storage time (P = 0.005) and severe agonal state (P = 0.02). Conclusion: Our data highlight the influence of pre‐ and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.     

Human class I major histocompatibility complex alleles determine central nervous system injury versus repair

Background

We investigated the role of human HLA class I molecules in persistent central nervous system (CNS) injury versus repair following virus infection of the CNS.

Methods

Human class I A11⁺ and B27⁺ transgenic human beta-2 microglobulin positive (Hβ2m⁺) mice of the H-2 ^b background were generated on a combined class I-deficient (mouse beta-2 microglobulin deficient, β2m⁰) and class II-deficient (mouse Aβ⁰) phenotype. Intracranial infection with Theiler’s murine encephalomyelitis virus (TMEV) in susceptible SJL mice results in acute encephalitis with prominent injury in the hippocampus, striatum, and cortex.

Results

Following infection with TMEV, a picornavirus, the Aβ⁰.β2m⁰ mice lacking active immune responses died within 18 to 21 days post-infection. These mice showed severe encephalomyelitis due to rapid replication of the viral genome. In contrast, transgenic Hβ2m mice with insertion of a single human class I MHC gene in the absence of human or mouse class II survived the acute infection. Both A11⁺ and B27⁺ mice significantly controlled virus RNA expression by 45 days and did not develop late-onset spinal cord demyelination. By 45 days post-infection (DPI), B27⁺ transgenic mice showed almost complete repair of the virus-induced brain injury, but A11⁺ mice conversely showed persistent severe hippocampal and cortical injury.

Conclusions

The findings support the hypothesis that the expression of a single human class I MHC molecule, independent of persistent virus infection, influences the extent of sub frequent chronic neuronal injury or repair in the absence of a class II MHC immune response.

     

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.     

Synthesis,biological evaluation,and molecular modeling of (<Emphasis Type="Italic">E</Emphasis>)-2-aryl-5-styryl-1,3,4-oxadiazole derivatives as acetylcholine esterase inhibitors

A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC₅₀ values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives.